Angiogenesis iruhibitors discovered in the laboratory are currently being translated to clhdcal application. At least 20 angiogenesis inhibitors are in clinical trial for the treatment of advanced cancer in more than 100 medical centers in the U.S. There is a need for a new understanding of antiangiogenic therapy in patients. Project 6 addresses three of these needs. We will determine whether lymphatic vessels in the tumor neighborhood are under similar regtflatory mechanisms as tumor angiogenesis. We will also determine whether angiogenesis hdfibitors simultaneously inhibit lymphangiogenesis. If not, we will then try to determine if separate molecules inhibit lymphangiogenesis. We have developed the first animal model that can dissociate lymphangiogenesis from angiogenesis in vivo in a quantitative way. A second part of this project will be to determine if levels of circulating progenitor endothelial cells correlate with onset or intensity of tumor angiogenosis. Furthermore, we will try to determine if circulating progenitor endothelial cells can be used to quantify early efficacy of anfiangiogomc therapy. A third part of the project will be a study of the regulation of aagiogenesis in endometfiosis. This represents a non-neoplastic disease which appears to be angiogenesis dependent. However, it behaves ha a malignant way with invasion of tissues and progression. We have developed an animal model, and we will atterapt to determine efficacy of anfiangiogeade therapy. The overall goal of this project is to increase our understanding of antiangiogenic therapy so that it can be used efficiently, both in neoplastic and non-neoplastic diseases in patients.